Article excerpt

Neural tube defects (NTDs) refer to a spectrum of adverse early prenatal development involving failure of normative neural tube closure within approximately 18-28 days post-conception (Botto, Moore, Khoury, & Erickson, 1999). The most prevalent are spina bifida and anencephaly and also include encephalocele, craniorachischisis, and iniencephaly (Kondo, Kamihira, & Ozawa, 2009). Folate is needed for the synthesis of purines and thymidylate that are essential for DNA synthesis and replication. Folate also appears crucial for epigenetic processes that regulate gene transcription and, in turn, the phenotype of species. Folic acid supplementation before and during pregnancy was first proposed to prevent NTDs in the 1960s by R.W. Smithells (Hibbard, 1964). Subsequent case-control and non-randomized prospective cohort studies in women who did not have previous NTD-birth outcomes, as well as non-randomized and randomized trials for women with prior NTD birth histories also showed substantial reported reductions in NTDs (Burdge & Lillycrop, 2012).

However, according to the British Scientific Advisory Committee on Nutrition (2006), the magnitude of real-world effects of folic acid supplementation has been less than anticipated from earlier research trials. These findings may be a consequence of unplanned pregnancies, which represent about 50 percent of pregnancies in the United States (Finer & Henshaw, 2006), and the fact that the overwhelming majority of women do not follow the recommended guideline that supplementation should commence well before instead of after conception (Crozier et al., 2009; Ray, Singh, & Burrows, 2004). Due to these risk factors, more than fifty countries have introduced or recommended mandatory fortification of processed grains since the 1990s, typically 40-220mg/100g. (Crider, Bailey, & Berry, 2011). Although the causal processes and etiology for neural tube defects (NTDs) are still largely unknown, national mandatory folic acid fortification of processed wheat grains has yielded increased serum folate status and NTD declines in those countries with fortification mandates. This includes the United States following its 1998 government mandate. This decline is especially significant in nations with the greatest incidences of NTDs (Crider, Bailey, & Berry, 2011).

However, other countries without imposed folic acid food fortification programs have also shown declines in the prevalence of NTDs worldwide during the past three decades (Osterhues, Ali, & Michels, 2013). Improved diagnostic imaging, use of bio-detectors like serum alpha-fetoprotein, increased acceptance of pregnancy termination, and fortification with folic acid in many countries are factors assumed to be responsible for the decline in NTDs in countries not requiring folic acid fortification. Other alternative explanations for the global decline may include overall improved diets, as well as the possibility that unpredictable waves of NTD prevalence with shifting peaks and nadirs may occur and account for some of the downward shifts in NTD rates coincidental with the recent prevention mandates. For example, Texas had inexplicably high rates of NTDs in the 1970s and again in the 1990s that eventually subsided (Suarez, et al., 2012). Much like episodes of viral outbreaks, what produces sudden spikes and subsequent declines in NTDs usually remains unknown. For example, in the United States post-fortification, a recent unexplained spike occurred in one region of Washington State (CDC, 2013; Wallis, 2014). To date, the Washington State spike appears unrelated to ethnicity, maternal diet, environment or any factors thought to be related to NTDs.

This troubling post-fortification spike in NTDs suggests that a caveat might be in order regarding the CDC's (2015) claim of overwhelming success for the 1998 FDA folic acid fortification mandate to reduce NTDs. While the efficacy of folic acid for preventing NTDs has been well-documented, the time frame of the CDC analysis may have exaggerated its efficacy. …